Abstract

IntroductionThe prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated.MethodsSeventy-three consecutive patients (median age, 61 years) with stage IIIB and IV non-small cell lung cancer, admitted between February 2004 and December 2006, were included in this study. Sixty-one patients received gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two 25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1. Both treatment paradigms were repeated on a 21-day cycle. Tumor response was evaluated by comparing tumor size on computerized tomography scans before and after three cycles of chemotherapy. HER2 status was examined by immunohistochemical analysis of paraffin-embedded specimens.ResultsHER2 was positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity, 13 (61.9%) responded to chemotherapy with either a complete response, partial remission, or evidence of stable disease. Of 52 HER2-negative patients, 48 (92.3%) exhibited a response to chemotherapy. The difference in response to therapy between HER2-positive and -negative patients was statistically significant (p = 0.003). The median overall survival duration for all patients was 13 months. Median overall survival time was 14 months for HER2-negative patients and 10 months for HER2-positive patients (log-rank p = 0.007).ConclusionNon-small cell lung cancer patients with high expression of HER2 exhibited resistance to cisplatin-based chemotherapies that are the standard treatment for this disease. Our results indicate that HER2 status may be a predictive and prognostic factor for cisplatin- based therapy response and disease survival.

Highlights

  • The prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial

  • The aim of the current study was to investigate the relationship between HER2 expression in non-small cell lung cancer patients, and to assess the effect of this expression on cisplatin-based chemoresistance

  • Patient characteristics Seventy-three patients with non-small cell lung cancer were evaluated between February 2004 and December

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Summary

Introduction

The prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated. Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide [1]. A combination of cisplatin or carboplatin with third generation agents, such as gemcitabine, paclitaxel, docetaxel, or vinorelbine, represents the standard of care for fit patients with advanced disease [35]. Appreciable clinical response to chemotherapy is achieved in only 30–40% of patients, probably because of relatively higher chemoresistance intrinsic to NSCLC. The mechanism of this resistance is not well understood. The therapeutic efficacy of anticancer agents is strongly dependent on the ability of the drugs to trigger apoptosis in target tumor cells [7]

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